Astragalus extract inhibits proliferation but enhances apoptosis in gastric cancer

Pak J Pharm Sci. 2016 Sep;29(5):1473-1482.

Abstract

We and others have shown that Astragalus extract (AE) regulates various cellular processes including inflammation and apoptosis. It remains elusive whether and how AE modulates apoptosis in gastric cancer cells in vitro and in vivo. The objective of this study is to determine the effects and mechanisms of AE on the proliferation and apoptosis of human gastric cancer SGC-7901 cells and on tumor growth in orthotopic transplantation gastric tumor model in nude mice. Human gastric adenocarcinoma SGC-7901 cells and nude mice implanted with gastric cancer cells were treated with different concentration of AE and 5-fluorouracil as control. Cellular proliferation, apoptosis and tumor growth as well as interleukin (IL)-6/signal transducer and activator of transcription (Stat) 3 signals pathway were determined. We found that AE inhibited proliferation but caused apoptosis in human gastric cancer cells. Furthermore, the tumor growth and volume were reduced by AE administration in nude mice implanted with gastric cancer cells. In addition, treatments with AE decreased the expression of Bcl-2 proteins, whereas the expression of Bax was increased after AE treatment in tumor tissues of nude mice transplanted with human gastric cancer cells. This was associated with AE-mediated reduction of IL-6, phosphorylated Stat3, survivin and vascular endothelial growth factor. Overall, AE enhances apoptosis in gastric cancer cells in vitro and in vivo, which is associated with decreased activation of IL-6/Stat3 signals.

Keywords: Astragalus extract; IL-6; STAT3; apoptosis; gastric cancer; vascular endothelial growth factor surviving..

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Astragalus Plant / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Survivin
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • BCL2 protein, human
  • BIRC5 protein, human
  • IL6 protein, human
  • Inhibitor of Apoptosis Proteins
  • Interleukin-6
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Survivin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A